Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that has been related not only to neurodevelopment and neuroprotection, but also to synapse regulation, learning, and memory. Research focused on the neurobiology of schizophrenia has emphasized the relevance of neurodevelopmental and neurotoxicity-related elements in the pathogenesis of this disease. Research focused on the clinical features of schizophrenia in the past decades has emphasized the relevance of cognitive deficits of this illness, considered a core manifestation and an important predictor for functional outcome. Variations in neurotrophins such as BDNF may have a role as part of the molecular mechanisms underlying these processes, from the neurodevelopmental alterations to the molecular mechanisms of cognitive dysfunction in schizophrenia patients.

The development of a neuron from a precursor cell comprises a complex set of steps ranging from regulation of the proliferative cycle through the acquisition of distinct morphology and functionality. How these processes are orchestrated is largely unknown. Using in utero manipulation of gene expression in the mouse embryonic cerebral cortex, we found that the transition between multipolar and bipolar stages of newborn cortical pyramidal neurons is markedly delayed by depletion of CoREST, a corepressor component of chromatin remodeling complexes. This profoundly affects the onset of their radial migration. The loss of CoREST function also perturbs the dynamics of neuronal precursor cell populations, transiently increasing the fraction of cells remaining in progenitor states, but not the acquisition of the neuronal glutamatergic fate of pyramidal cells. The function of CoREST in these processes appears to be independent of its best-known interactor, the RE-1 silencer of transcription/neural restrictive silencing factor, and requires the histone demethylase LSD1. This reveals the importance of epigenetic control in the execution of neural development programs, specifically in the cerebral cortex.

Drosophila discs-large (dlg) mutants exhibit multiple developmental abnormalities, including severe defects in neuronal differentiation and synaptic structure and function. These defects have been ascribed to the loss of a single gene product, Dlg-A, a scaffold protein thought to be expressed in many cell types. Here, we describe that additional isoforms arise as a consequence of different transcription start points and alternative splicing of dlg. At least five different dlg gene products are predicted. We identified a subset of dlg-derived cDNAs that include novel exons encoding a peptide homologous to the N terminus of the mammalian protein SAP97/hDLG (S97N). Dlg isoforms containing the S97N domain are expressed at larval neuromuscular junctions and within the CNS of both embryos and larvae but are not detectable in epithelial tissues. Strong hypomorphic dlg alleles exhibit decreased expression of S97N, which may account for neural-specific aspects of the pleiomorphic dlg mutant phenotype. Selective inhibition of the expression of S97N-containing proteins in embryos by double-strand RNA leads to severe defects in neuronal differentiation and axon guidance, without overt perturbations in epithelia. These results indicate that the differential expression of dlg products correlates with distinct functions in non-neural and neural cells. During embryonic development, proteins that include the S97N domain are essential for proper neuronal differentiation and organization, acting through mechanisms that may include the adequate localization of cell fate determinants.

Pituitary gonadotrophs exhibit spontaneous low-amplitude fluctuations in cytoplasmic calcium concentration ([Ca2J] and prolactin release in vitro (7). The actions of several hypothalamic neurohormones, such as growth hormonereleasing hormone, corticotropin-releasing factor, somatostatin, and dopamine, include facilitation or inhibition of the basal-membrane oscillatory activity (5,(8)(9)(10)(11)